Treatment with plasma exchange of a pregnant woman with anti-PP1Pk alloimmunization: A case report.

The histo-blood group antigens P, P1 and Pk are a closely related set of glycosphingolipid structures expressed by red blood cells and other tissues. None of these three characters is expressed on p cells, a null phenotype that arises in the context of homozygous mutation of the A4GALT gene. Subjects with p phenotype spontaneously develop a natural alloantibody named anti-PP1Pk, which is a mixture of IgG and IgM against P1, P and Pk. While anti-P1 is a weak cold antibody with poor clinical significance, anti-P and anti-Pk antibodies are potent haemolysins responsible for severe hemolytic transfusion reactions. The rare anti-PP1Pk alloantibodies are associated with recurrent spontaneous abortion in the first trimester of gestation. P and Pk antigens are expressed at high levels on the placenta and antibodies directed against both these structures are deleterious to placental trophoblasts. Here we describe the use of plasma exchange (PEX) in a nulliparous 39-year-old woman with anti-PP1Pk antibodies and a history of repeated spontaneous early abortions and hypofertility. The patient underwent apheresis starting from the third week throughout the pregnancy and a healthy child was delivered by cesarean section at 35 WG. The newborn required only phototherapy within a few days of life. We can state that an early treatment with the only PEX has proven to be effective and safe in the management of a fetomaternal P-incompatibility caused by a high anti-PP1Pk titer (256).

[Splenic lymphoma, diagnosis and treatment]. / Lymphomes spléniques : diagnostic et prise en charge.

Some common clinical situations, such as splenomegaly or lymphocytosis, or less common, such as autoimmune hemolytic anemia, cold agglutinin disease, or cryoglobulinemia can lead to the diagnosis of splenic lymphoma. Splenic lymphoma is rare, mainly of non-hodgkinian origin, encompassing very different hematological entities in their clinical and biological presentation from an aggressive form such as hepato-splenic lymphoma to indolent B-cell lymphoma not requiring treatment such as marginal zone lymphoma, the most frequent form of splenic lymphoma. These entities can be challenging to diagnose and differentiate. This review presents different clinical and biological manifestations suspicious of splenic lymphoma and proposes a diagnosis work-up. We extended the strict definition of splenic lymphoma (lymphoma exclusively involving the spleen) to lymphoma thant can be revealed by a splenomegaly and we discuss the differential diagnosis of splenomegaly.

Outcome predictors for maternal red blood cell alloimmunisation with anti-K and anti-D managed with intrauterine blood transfusion.

Red blood cell (RBC) alloimmunisation with anti-D and anti-K comprise the majority of cases of fetal haemolytic disease requiring intrauterine red cell transfusion (IUT). Few studies have investigated which haematological parameters can predict adverse fetal or neonatal outcomes. The aim of the present study was to identify predictors of adverse outcome, including preterm birth, intrauterine fetal demise (IUFD), neonatal death (NND) and/or neonatal transfusion. We reviewed the records of all pregnancies alloimmunised with anti-K and anti-D, requiring IUT over 27 years at a quaternary fetal centre. We reviewed data for 128 pregnancies in 116 women undergoing 425 IUTs. The median gestational age (GA) at first IUT was significantly earlier for anti-K than for anti-D (24·3 vs. 28·7 weeks, P = 0·004). Women with anti-K required more IUTs than women with anti-D (3·84 vs. 3·12 mean IUTs, P = 0·036) and the fetal haemoglobin (Hb) at first IUT was significantly lower (51.0 vs. 70.5 g/l, P = 0·001). The mean estimated daily decrease in Hb did not differ between the two groups. A greater number of IUTs and a slower daily decrease in Hb (g/l/day) between first and second IUTs were predictive of a longer period in utero. Earlier GA at first IUT and a shorter interval from the first IUT until delivery predicted IUFD/NND. Earlier GA and lower Hb at first IUT significantly predicted need for phototherapy and/or blood product use in the neonate. In the anti-K group, a greater number of IUTs was required in women with a higher titre. Furthermore, the higher the titre, the earlier the GA at which an IUT was required in both groups. The rate of fall in fetal Hb between IUTs decreased, as the number of transfusions increased. Our present study identified pregnancies at considerable risk of an unfavourable outcome with anti-D and anti-K RBC alloimmunisation. Identifying such patients can guide pregnancy management, facilitates patient counselling, and can optimise resource use. Prospective studies can also incorporate these characteristics, in addition to laboratory markers, to further identify and improve the outcomes of these pregnancies.

Cold agglutinin disease and COVID-19 requiring therapeutic plasma exchange.

A 70-year-old man with known cold autoimmune haemolytic anaemia was referred to the emergency department with increased shortness of breath on exertion. He had been confirmed positive for non-variant COVID-19 infection 1 week earlier based on nasopharyngeal swab PCR assay. CT thorax demonstrated diffuse patchy bilateral ground glass opacities, consistent with COVID-19 pneumonia. Bloodwork demonstrated severe cold agglutinin mediated haemolytic anaemia. To help stabilise the patient, he was transferred to a tertiary care hospital for urgent therapeutic plasma exchange. Key supportive therapy included folic acid supplementation, ensuring the patient was kept warm and warmed infusions including transfusions via the apheresis machine. The patient made a good recovery following plasma exchange, and his haemoglobin levels remained stable by discharge.

Anti-plasma cell treatment in refractory autoimmune hemolytic anemia in a child with multivisceral transplant.

BACKGROUND: Warm-antibody AIHA is known to complicate solid organ (SOT) and HSCT, the disease maybe refractory to standard therapy. Immunosuppressive therapies as well as IVIG, and rituximab have been the main stay of treatment. Over the past decade, B-lymphocyte targeted, anti-CD-20 antibody has been recognized in the treatment of autoimmune diseases and utilized in AIHA. Bortezomib, a proteasome inhibitor that causes apoptosis of plasma cells, is an appealing targeted therapy in secondary AIHA and has demonstrated efficacy in HSCT patients. From our experience, we advocate for early targeted therapy that combines B cell with plasma cell depletion. CASE REPORT: We describe a 4-year-old-girl with stage III neuroblastoma, complicated with intestinal necrosis needing multivisceral transplant developed warm AIHA 1-year after transplantation, and following an adenovirus infection. She received immunoglobulin therapy, rituximab, sirolimus, plasmapheresis, and long-term prednisolone with no sustained benefit while developing spinal fractures related to the latter therapy. She received bortezomib for intractable AIHA in combination with rituximab with no appreciable adverse effects. Three years later the child remains in remission with normal reticulocyte and recovered B cells. In the interim, she required chelation therapy for iron overload related to blood transfusion requirement during the treatment of AIHA. CONCLUSION: We propose early targeted anti-plasma cell therapy with steroid burst, IVIG, rituximab, and possible plasmapheresis may reduce morbidity in secondary refractory w-AIHA.

Complications of a severe autoimmune hemolytic anemia crisis: transfusional iron overload and gangrenous cholecystitis.

BACKGROUND: Evans syndrome is a rare autoimmune disorder that is defined by the simultaneous or sequential presence of two or more cytopenias without an obvious underlying precipitating cause. Evans syndrome usually follows a chronic relapsing and remitting course and is quite rare, making it difficult to evaluate in clinical studies. CASE REPORT: A 66-year-old male patient with a 17-year history of Evans syndrome presented with fulminant autoimmune hemolytic anemia (AIHA). He presented with a markedly elevated C-reactive protein (CRP; 46 mg/L [normal, 0-5 mg/L]) before onset of a decrease in hemoglobin. He required the transfusion of 20 units of red blood cells while awaiting response to aggressive immunosuppressive therapy including high-dose corticosteroids, intravenous immunoglobin therapy, and rituximab. He achieved a complete hematologic response. RESULTS: His postdischarge course was complicated by acute cholecystitis requiring laparoscopic cholecystectomy. In addition, his transfusional iron overload requiring 16 phlebotomies to reduce his ferritin level from 4933 µg/L to 326 µg/L, with phlebotomies ongoing every 2 weeks to achieve a ferritin level of less than 100 µg/L. CONCLUSION: Neither transfusional iron overload nor acute cholecystitis are well-recognized complications of a severe episode of AIHA. An elevated CRP has been recently recognized as an important prognostic marker in patients with immune thrombocytopenic purpura and this case suggests a need to evaluate its utility in AIHA.

Benefits of Delayed Cord Clamping in Red Blood Cell Alloimmunization.

BACKGROUND AND OBJECTIVE: Several studies have shown the benefits of delayed cord clamping (DCC) in preterm and in healthy newborns at short and long term. Our objective was to evaluate the potentials benefits and risks of DCC in red cell alloimmunization. METHODS: This was a comparative before/after study of all living born neonates followed after fetal anemia requiring in utero transfusion. DCC was defined as cord clamping 30 seconds after birth. RESULTS: We included a continuous series of 72 neonates: 36 without DDC (group 1) and 36 with DDC (group 2). Hemoglobin at birth was lower in group 1 (10.2 vs 13.4 g/dL, P = .0003); 7 (25%) neonates in group 1 vs 24 (70.6%) in group 2 had no anemia at birth (P = .004). The rate of transfusion was similar between the 2 groups. Postnatal exchange transfusions were more likely performed in the group without DCC than in the group with DCC (47.2% vs 19.4%, P = .0124). Delay between birth and first transfusion was higher in group 2 (0 [0-13] vs 1 [0-21], P = .0274). The maximum level of bilirubin, the rate of intensive phototherapy, and the total duration of phototherapy were similar in the 2 groups. CONCLUSIONS: This study highlights a significant benefit of DCC in anemia secondary to red blood cell alloimmunization with a resulting decreased postnatal exchange transfusion needs, an improvement in the hemoglobin level at birth and longer delay between birth and first transfusion with no severe hyperbilirubinemia.

Red Blood Cell Transfusion in Patients With Autoantibodies: Is It Effective and Safe Without Increasing Hemolysis Risk?

BACKGROUND: The therapeutic efficacy of red blood cell (RBC) transfusions in patients with autoimmune hemolytic anemia (AIHA) is highly debated because of speculations on the increased risk of transfusion reactions; yet it is a suggested adjuvant therapy in anemic patients with life-threatening hypoxemia. In this study, we evaluated the safety and efficacy of RBC transfusions in AIHA patients. METHODS: Daily changes in hemoglobin, total bilirubin, and lactate dehydrogenase (LDH) were assessed in 161 AIHA patients without bleeding history who were transfused once with 1-5 units of the least-incompatible RBCs and monitored over a seven-day period. Post-transfusion patients positive for alloantibodies only or those without RBC-specific antibodies were considered as control groups (N=100 for both groups). RESULTS: The three groups revealed similar increases in hemoglobin of 1.40-1.70 g/dL (autoantibodies), 1.20-1.60 g/dL (alloantibodies only), and 1.40-1.55 g/dL (no antibodies) for seven days following transfusion of 10 mL RBCs/kg. During follow-up, no significant changes in total bilirubin or LDH levels were detected in the AIHA group compared with controls. Influences due to autoantibody type, direct antiglobulin test (DAT) specificity and strength, and steroid therapy status on transfusion reactions were not evident in AIHA patients. In addition, changes in hemoglobin levels were significantly higher (P<0.001) in severe anemia (<5 g/dL) than in other patients. CONCLUSIONS: Transfusion of the least-incompatible RBCs in AIHA patients is effective and safe without any associated increase in hemolysis risk when compared with post-transfusion patients positive for alloantibodies or those lacking RBC-specific antibodies.

Purpuric eruption in a transfused neonate receiving phototherapy.

We describe the clinical and biochemical findings in a neonate requiring multiple blood transfusions and phototherapy for alloimmune hemolytic anemia and unconjugated hyperbilirubinemia, respectively. In this newborn, a severe photosensitivity reaction developed and laboratory testing revealed elevated serum and urine porphyrins at the time of the eruption. The cause of the transient porphyrinemia was likely multifactorial. Possible mechanisms include poor hepatic metabolism and reticulocyte hemolysis. However, the exact pathogenesis remains unclear at this time.

Intravenous immunoglobulin to treat neonatal alloimmune haemolytic disease.

OBJECTIVE: To compare the efficacy of intravenous immunoglobulin (IVIg) and exchange transfusion (EXT) on rhesus haemolytic disease of the newborn (Rh-HDN) and evaluate treatment-related side effects. METHODS: Retrospective chart review of two cohorts of newborns with Rh-HDN, treated with (Group 2) or without (Group 1) IVIg. Length of phototherapy, number of EXT, IVIg infusions, intrauterine and top-up red blood cells transfusions, need and permanence of umbilical venous catheter, and length of hospital stay, as well as treatment-related adverse events, were evaluated. RESULTS: Charts of 88 newborns were reviewed (34 in Group 1, 54 in Group 2). Infants in Group 2 received a significantly lower number of EXT, had a lower risk of neurological impairment and needed an umbilical venous catheter for shorter, but required longer phototherapy, longer length of hospital stay, and more top-up transfusions. EXT was associated with a high number of adverse events. Two newborns treated with IVIg developed necrotizing enterocolitis (NEC). CONCLUSIONS: IVIg appear as an effective alternative to EXT, reducing the risk of neurological impairment and complications related to EXT. However, side effects of IVIg treatment (higher need of top-up transfusions and longer hospital stay) should be taken into account and the risk of NEC should be carefully monitored during treatment.

[A woman in her 60s with multifactorial anaemia]. / En kvinne i 60-årene med kombinert anemi.

Anaemia may be multifactorial in origin. We present a woman with autoimmune hepatitis and secondary warm autoimmune haemolytic anaemia and most likely also concomitant anaemia of chronic disease. A relapse of autoimmune haemolysis was successfully treated with steroids and high-dose intravenous immunoglobulin. At the same time, bleeding from angiodysplasia in the coecum was masked by unauthorised perorally administrated iron. No other cause of bleeding was found. During that period, she required extensive blood transfusions, up to several times per month. Surgical or endoscopic treatment of the bleeding angiodysplasia was not possible. Alloimmunisation developed as a complication to the large number of transfusions, despite the use of steroids. Treatment with somatostatin analogue markedly reduced the need of our patient for blood transfusions for a follow-up period of more than one year, and she has not experienced any side effects. We do not know how long the haemostasis achieved will last, however, we believe that this treatment may be an alternative for other patients as bleeding from angiodysplasia is not uncommon and is often difficult to eradicate.

First-line stereotactic treatment of thalamic abscesses: report of three cases and review of the literature.

Solitary pyogenic thalamic and basal ganglia abscesses are relatively uncommon. Even if widespread antibiotic therapy and modern imaging technologies combined with minimally invasive techniques have improved the outcome in patients with brain abscesses, this is counterbalanced by an increasing population of immunocompromised patients. Basal ganglia, thalamic, brainstem or multiple abscesses are usually of hematogenous origin with an underlying source of infection which can include congenital heart disease, thoracic sepsis or, less frequently, an odontogenic or otogenic source. However, no evident foci of sepsis or predisposing factors may be found. Only a few studies are reported in the literature, because midline abscesses are usually included in studies dealing on the treatment of abscesses in general. Different treatment options and the timing of treatment are described. We report our experience in 3 consecutive cases of thalamic abscess, treated by stereotactic puncture as the first step, followed by histological analysis, external drainage and targeted intrathecal and systemic antibiotic therapy. Deep-seated abscesses seem to behave differently as they are associated with an increased risk of intraventricular rupture and antibiotic resistance, a fact which justifies a more aggressive and immediate surgical treatment. We review the literature on this topic in the last 20 years.

Use of therapeutic plasmapheresis in a case of canine immune-mediated hemolytic anemia.

OBJECTIVE: To investigate the clinical application and potential utility of plasmapheresis in canine immune-mediated hemolytic anemia. CASE SUMMARY: A 7-year-old spayed female Maltese diagnosed with immune-mediated hemolytic anemia was initially treated with prednisone, cyclosporine, and received multiple transfusions of packed RBC. Because of the progression of clinical signs despite traditional medical therapy, plasmapheresis was initiated. Plasma immunoglobulin G and immunoglobulin M levels were measured before, during, and after treatment to help determine if there had been a significant decrease in immunoglobulin levels with plasmapheresis. Plasmapheresis was successfully performed over a 2.5-hour period in this dog with minimal complications. Hypocalcemia was identified as a known complication of circuit anticoagulation, and was corrected through calcium supplementation. Post-plasmapheresis there was a decrease in immunoglobulin G and immunoglobulin M levels, and the patient showed clinical improvement. Following discharge the dog had no known complications of therapy, and had complete resolution of the anemia. NEW OR UNIQUE INFORMATION PROVIDED: Plasmapheresis was performed successfully with minimal complications. Because transfusion requirements appeared to be reduced, and the procedure was well tolerated, there may be a place for this modality in severe cases to act as a bridge until medical therapy takes full effect. Because of the cost of performing this therapy, and the potential requirement for multiple treatments, it should be reserved for selected patients.

A case of rhesus hemolytic disease with hemophagocytosis and severe iron overload due to multiple transfusions.

BACKGROUND: A newborn with cholestatic hepatic disease and hemophagocytic lymphohistiocytosis due to rhesus hemolytic disease (RHD) is reported. OBSERVATION: A 34 weeks' gestation baby with RHD, who had received multiple intrauterine transfusions (IUT), developed cholestatic hepatic disease and secondary hemophagocytic lymphohistiocytosis (HLH). Her serum ferritin level increased to 5,527 ng/mL, and liver biopsy showed severe iron overload. Treatment with intravenous desferrioxamine resulted in a marked decrease in serum ferritin levels and normalization of liver function CONCLUSION: We suggest that patients who have undergone IUT be evaluated for hyperferritinemia. If hyperferritinemia is noted, chelation therapy should be considered. As another rare finding, HLH can complicate the course of RHD.

Multiple dose IVIG treatment in neonatal immune hemolytic jaundice.

Isoimmune hemolytic jaundice due to ABO and Rh blood group incompatibility is an important problem in the neonatal period. Intravenous immune globulin (IVIG) treatment in isoimmune jaundice has been shown to be effective, but the response to treatment is variable. In this study, the effect of multiple doses IVIG therapy versus single dose MG therapy was investigated in 61 babies who had ABO and Rh hemolytic disease. Patients were divided into three groups. Group I received multiple dose IVIG treatment, group II received single dose MG treatment, and group III was not given any IVIG. All three groups received phototherapy. No exchange transfusion was needed in group I. The rate of exchange transfusion was 12 per cent in group II and 33 per cent in group III. Duration of phototherapy was shorter in group I than in groups II and III. It was concluded that IVIG treatment reduces the need of exchange transfusion in neonatal isoimmune hemolytic jaundice by lowering hemolysis. Multiple doses IVIG treatment appears to be better at blocking ongoing hemolysis.

Overproduction of antiplatelet antibody against glycoprotein IIb after splenectomy in a patient with Evans syndrome resulting in acquired thrombasthenia.

We treated a 33-year-old female with Evans syndrome. She received high dose gamma globulin, prednisolone, and azathioprine, and her platelet count transiently increased. After splenectomy, the platelet count markedly increased. However, the bleeding tendency worsened and the bleeding time was prolonged. A platelet defect, characteristic of thrombasthenia, was found. Antigen-captured ELISA and Western blotting revealed that the patient's serum had an IgG autoantibody against platelet membrane glycoprotein IIb and the patient's plasma inhibited normal platelet aggregation. These findings suggest that overproduction of the antiplatelet antibody is triggered by platelet recovery due to splenectomy and affects platelet function resulting in acquired thrombasthenia.

Tratamiento homeopatico de un caso de anemia hemolitica autoinmune / Homeopathic treatment of a case of autoimune hemolytic anemia

En el presente articulo, se comunica el tratamiento homeopatico de un caso de Anemia Hemolitica Autoimune, prescindiendo de drogas inmunosupresoras

Tratamiento homeopatico de un caso de anemia hemolitica autoinmune / Homeopathic treatment of a case of autoimune hemolytic anemia

En el presente articulo, se comunica el tratamiento homeopatico de un caso de Anemia Hemolitica Autoimune, prescindiendo de drogas inmunosupresoras

Tratamiento homeopatico de un caso de anemia hemolitica autoinmune / Homeopathic treatment of a case of autoimune hemolytic anemia

En el presente articulo, se comunica el tratamiento homeopatico de un caso de Anemia Hemolitica Autoimune, prescindiendo de drogas inmunosupresoras